Rheumatoid arthritis: pregnancy - 1 File Download



Extractable nuclear antigensspecific nuclear antigensusually associated with being ANA positiveExamplesAnti-Ro Sjogren's syndrome/ SLE/ congenital heart blockAnti-La Sjogren's syndromeAnti-Jo1 polymyositisAnti-scl-70 diffuse cutaneous systemic sclerosisAnti-Centromere limited cutaneous systemic sclerosisSeronegative spondyloarthropathiesAssociated with HLA-B27Rh. Factor negative 'Seronegative'Peripheral arthritis usually asymmetricalSacroiliitisEnthesopathy Achilles tendonitis, plantar fasciitisExtra-Articular manifestations Uveitis, Pulmonary Fibrosis (upper zone), Amyloidosis, Aortic RegurgitationSpondyloarthropathiesAnkylosing SpondylitisPsoriatic ArthritisReiter's Syndrome (including reactive arthritis)Enteropathic Arthritis (associated with IBD)There is an indirect association between HLA-B27 and Crohn's as some patients may develop Enteropathic arthritis, but this is the least common association of the aboveRheumatoid arthritisThe most important Cytokines in the pathophysiology TNF (pro-inflammatory cytokine.mainly by macrophages and acting mainly in a paracrine fashion:(++) Macrophages and Neutrophilsacts as costimulator for T cell activationkey mediator of bodies response to Gram negative septicaemiaSimilar properties to IL-1Anti-tumour effect (Phospholipase Activation)TNF-alpha binds to both the p55 and p75 receptor. These receptors can induce apoptosis. It also cause activation of NFkBEndothelial effects ↑↑ (expression of selectins, platelet activating factor, IL-1 and prostaglandins)(+ +) Proliferation of fibroblasts, protease and Collagenase (fragments of receptors act as binding points in serum)Systemic effects pyrexia,↑↑ acute phase proteins and disordered metabolism leading to cachexiaImportant in the pathogenesis of RA TNF blockers (infliximab, etanercept) are now licensed for treatment of severe rheumatoidEpidemiology Peak onset = 30-50 years, although occurs in all age groupsF:M ratio = 3:1prevalence = 1%↑↑ Native Americansassociated with HLA-DR4 (especially Felty's syndrome)Ocular manifestations of rheumatoid arthritis are common, with 25% of patients having eye problemskeratoconjunctivitis sicca (most common)episcleritis (erythema)scleritis (erythema and pain)corneal ulcerationkeratitisIatrogenicsteroid-induced cataractschloroquine retinopathyComplicationsA wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA):Respiratory pulmonary fibrosis, pleural effusion, Pulmonary nodules, bronchiolitis obliterans, methotrexate pneumonitis, pleurisyEye keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration, keratitis, steroid-induced cataracts, Chloroquine retinopathyOsteoporosisCVS RA carries a similar risk to type 2 D.M↑↑ risk of infectionsCNS DepressionLess commonFelty's syndrome (RA + Splenomegaly + ↓↓ WBCs)AmyloidosisInvestigtion (Anti-bodies)Rheumatoid factorCirculating antibody (usually IgM) reacts with the Fc portion of the patients own IgG. detected by eitherRose-Waaler test: sheep red cell agglutinationLatex agglutination test (less specific)+Ve 70-80% (↑↑ levels are associated with severe progressiveD) but NOT a marker of disease activityOther conditions associated with a positive RF include:Sjogren's syndrome (100%)Felty's syndrome (100%)Infective endocarditis (50%)SLE (20-30%)Systemic sclerosis (30%)general population (5%)rarely: TB, HBV, EBV, leprosyAnti-cyclic citrullinated peptide antibodyDetectable up to 10 years before the development RA. allowing early detection of patients suitable for aggressive anti-TNF therapy. Similar sensitivity to rheumatoid factor (around 70%) + ↑↑ specificity of 90-95%. For suspected RA W (–Ve Rheumatoid factor).X-Ray ChangesEarly x-ray findingsLate x-ray findingsloss of joint spacejuxta \Peri -articular Osteoporosis/Osteopenia) Characterize RAsoft-tissue swellingPeriarticular erosionssubluxationManagementEvidence of joint inflammation start a combination of disease-modifying drugs (DMARD) ASAP.-/+ analgesia, physiotherapy and surgery.Initial therapyDMARD?monotherapy?+/- a short-course of bridging Prednisolone. Monitoring response Combination (CRP + Disease Activity (using a composite score "DAS28").Flares Corticosteroids (Oral or IM)DMARDsMethotrexate is the most widely usedMonitoring of FBC & LFTs ( Risk of myelosuppression and liver cirrhosis). Other S/E include PneumonitisSulfasalazineManagement of inflammatory arthritis(RA) and IBD Prodrug for 5-ASA? ↓↓neutrophil chemotaxis + (--) proliferation of lymphocytes and pro-inflammatory cytokines.Cautions G6PD deficiency & allergy to aspirin?or?sulphonamides?(cross-sensitivity)safe to use in both pregnancy and breastfeeding.Adverse effectsOligospermiaStevens-Johnson syndromePneumonitis / lung fibrosisMyelosuppression, Heinz body anaemia, megaloblastic anaemiaMay colour tears → stained contact lensesLeflunomideHydroxychloroquine AzathioprineMetabolized to the active compound mercaptopurine (Purine analogue that inhibits purine synthesis). A?thiopurine methyltransferase (TPMT)?test may be needed to look for individuals prone to azathioprine toxicity.Adverse effects includebone marrow depressionnausea/vomitingpancreatitis↑↑risk of non-melanoma skin cancerDrug interaction significant with?allopurinol? lower doses of azathioprine should be used.Azathioprine is generally considered safe to use in pregnancy Hydroxychloroquine Management of rheumatoid arthritis and systemic/discoid lupus erythematosus. very similar to chloroquine Adverse effectsbull's eye retinopathy - may result in severe and permanent visual lossMore common recently Colour retinal photography + Spectral domain optical coherence tomography scanning of the maculaBaseline ophthalmological examination?and annual screening is generally recommenedA contrast to many drugs used in rheumatology, hydroxychloroquine may be used if needed in pregnant women.Monitoring Ask patient about visual symptoms and monitor visual acuity annually using the standard reading chart' LeflunomideDisease modifying anti-rheumatic drug (DMARD) management of RA. It has a very long half-life and teratogenic potential.ContraindicationsPregnancy Effective contraception (plasma concentration monitoring required' during treatment and for at least 2 years after treatment in women at least 3 months after treatment in men Caution with pre-existing lung and liver diseaseAdverse effectsgastrointestinal, especially diarrhoeaHypertensionmyelosuppressionPneumonitis weight loss/anorexiaperipheral neuropathyMonitoringFBC/LFT and blood pressureStoppingleflunomide has a very long wash-out period of up to a year which requires co-administration of cholestyramineTNF-inhibitorsIndication inadequate response to at least two DMARDs including MethotrexateEtanerceptRecombinant human fusion protein (decoy receptor for TNF-α) S.C administrationS/E demyelination, risks include?reactivation of T.BInfliximabMonoclonal antibody (binds to TNF-α and prevents it from binding with TNF receptors) I.V administrationS/E reactivation of T.BIdalimumabMonoclonal antibody, S.C administrationRituximabAnti-CD20 monoclonal antibody B-cell depletiontwo 1g IV infusions 2weeks apartinfusion reactions are commonAbataceptFusion protein modulates a key signal required for activation of T lymphocytes ↓↓ T-cell proliferation and cytokine given as an infusionnot currently recommend by NICEPoor prognostic featuresRh. factor +VeAnti-CCP +VeHLA DR4Insidious onsetPoor functional status at presentationX-ray early erosions (after < 2 years)Extra articular features nodulesFemale gender (debatable) Rheumatoid arthritis: pregnancyRA typically develops in women of a reproductive age. patients with early or poorly controlled RA defer conception until their disease is more stableSymptoms tend to improve in pregnancy but only resolve in a small minority. Patients tend to have a flare following deliveryMethotrexate is not safe in pregnancy and needs to be stopped at least 6 months before conceptionleflunomide is not safe in pregnancySulfasalazine and Hydroxychloroquine Safe in pregnancyAnti-TNF agents infliximab and adalimumab not known to cause harm but (insufficient data) Cross the placenta in high doses in the third trimester.low-dose corticosteroids used in pregnancy to control symptomsNSAIDs may be used until 32 weeks but after this time should be withdrawn due to the risk of early close of the ductus arteriosusObstetric anaesthetist due to the risk of atlanto-axial subluxation Psoriatic arthropathyPsoriatic arthropathy correlates poorly with cutaneous psoriasis development of skin lesions. 10-20% with skin lesions develop an Arthropathy, males = females TypesRheumatoid-like polyarthritis: (30-40%, most common type)Asymmetrical Oligoarthritisaffects hands and feet (20-30%) more in line with PAuveitis and achilles tendonitis, synovitis, sacroiliitis, Dactylitis, enthesitis, Nail disease (Yellow& pitted) and SacroilitisDIP joint disease?(10%) DIP and Dactylitis (Whole digit is swollen along its length )↑↑common in psoriatic arthritis (DD. RA)X-ray (large eccentric erosions, tuft resorption and progresion towards 'pencil-in-cup' changes.Arthritis Mutilans (severe deformity fingers/hand, 'Telescoping Fingers')Managementshould be managed by a?rheumatologistTreat as rheumatoid arthritis but?better prognosisSystemic lupus erythematosus: A multisystem, autoimmune Type 3 hypersensitivity (immune complex formation) W HLA B8, DR2, DR3immune complex deposition can affect any organ including the skin, joints, kidneys and brain20-40 and is ↑↑women (9:1) and people of Afro-Caribbean (African < American) & Asian origin.FeaturesPhotosensitive Rash + Reynaud's Syndrome + Small joint arthritis likely diagnosis of systemic lupus erythematosus (SLE).?General FatigueFeverMouth ulcersLymphadenopathySkinMalar (butterfly) rash: Spares nasolabial foldsDiscoid rash Scaly, Erythematous, well demarcated rash in sun-exposed areas. Lesions may progress to become pigmented and Hyperkeratotic before becoming atrophicphotosensitivityReynaud's phenomenonlivedo Reticularisnon-scarring alopeciaMusculoskeletalarthralgianon-erosive arthritisCardiovascularpericarditis: the most common cardiac manifestationmyocarditisRespiratorypleurisyFibrosing alveolitisRenalproteinuriaGlomerulonephritis (diffuse proliferative glomerulonephritis is the most common type)Neuropsychiatricanxiety and depressionpsychosisseizuresinvestigationsImmunology99% are ANA positiveAnti-dsDNA highly specific (> 99%), but less sensitive (70%) highly associated with glomerulonephritis in SLE.Anti-Smith Most specific (> 99%), sensitivity (30%),20% are rheumatoid factor positivealso: anti-U1 RNP, SS-A (anti-Ro) associated with congenital heart block? (detect fetal and SS-B (anti-La)Anti-histone is associated with drug-induced lupus.MonitoringESR: during active disease the CRP is characteristically normal - a raised CRP may indicate underlying infection↓↓(C3, C4) during active disease (formation of complexes leads to consumption of complement)anti-dsDNA titres can be used for disease monitoring (but note not present in all patients)Drug-induced lupus Not all the typical features of SLE are seen (Kidney and CNS involvement are unusual) It usually resolves on stopping the drug.Arthralgia, myalgiaskin (Malar Rash) Pulmonary involvement (pleurisy) are commonAntibodies Association ANA positive in 100%,Anti-Histone Abs 80-90%Anti-Ro, Anti-Smith around 5%dsDNA negativeMost common causesLess common causesProcainamideHydralazineIsoniazidMinocyclinePhenytoinDiscoid lupus erythematosus A benign disorder seen in younger females. Characterized by follicular keratin plugs and is thought to be autoimmune in aetiology Very rarely progresses to SLE (< 5%). FeaturesRash raised Erythematous sometimes scalymay be photosensitivemore common on face, neck, ears and scalplesions heal with atrophy, scarring (may cause scarring alopecia), and pigmentationManagementTopical steroid creamOral antimalarials may be used second-line e.g. hydroxychloroquineAvoid sun exposureSystemic lupus erythematosus: pregnancyrisk of maternal autoantibodies crossing the placentaleads to a condition termed neonatal lupus erythematosusneonatal complications include?congenital heart blockstrongly associated withanti-Ro (SSA) antibodiesAntiphospholipid syndromeacquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE)A key point for the exam is to appreciate that antiphospholipid syndrome causes a paradoxical rise in the APTT. This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascadeLupus anticoagulant is the strongest risk factor for thrombosis of all the listed options Odds ratio for thrombosis 5 to 16 times higher than controls. Anticardiolipin antibodies, beta-2-glycoprotein 1 antibodies and the other options listed, are not considered as prothrombotic as lupus anticoagulant.Featuresvenous/arterial thrombosisrecurrent fetal losslivedo reticularisthrombocytopeniaprolonged APTTother features: pre-eclampsia, pulmonary hypertensionAssociations other than SLEother autoimmune disorderslymphoproliferative disordersphenothiazines (rare)Management initial venous thromboembolic events: warfarin with a target INR of 2-3 for 6 monthsRecurrent venous thromboembolic lifelong warfarin; if occurred whilst taking warfarin then increase target INR to 3-4arterial thrombosis lifelong warfarin with target INR 2-3Raynaud's phenomena 1ry (Raynaud's disease" young women (30 years old) with bilateral symptoms".) OR 2ry (Raynaud's phenomenon)? Factors suggesting underlying connective tissue diseaseonset > after 40 yearsunilateral symptomsRashes+Ve autoantibodiesfeatures suggests RA or SLE (arthritis OR Recurrent miscarriages)Digital ulcers Calcinosisvery rarely: chilblains (pernio) itchy, painful purple swellings on the fingers and toes after cold exposure. 2ry causesC.T disordersSystemic Sclerosis (2%) of women and (6%) of men with Raynaud's phenomenon develop systemic sclerosis (most common),RA, SLELeukaemiaType I cryoglobulinaemia, cold agglutininsUse of vibrating toolsDrugs Oral Contraceptive Pill, ErgotCervical ribManagementall patients with suspected?secondary Raynaud's phenomenon should be referred to secondary carefirst-line calcium channel blockers (Nifedipine)IV Prostacyclin (Epoprostenol) infusions: effects may last several weeks/monthsSjogren's syndrome Autoimmune disorder affecting exocrine glands? dry mucosal surfaces. 1ry (PSS) or 2ry to RA OR other C.T disorders, where it usually develops around 10 years after the initial onset.Much more common in females (ratio 9:1). There is a?marked increased risk of Lymphoid malignancy (40-60 folds)FeaturesDry Eyes Keratoconjunctivitis SiccaDry Mouth (Xerostomia)Recurrent episodes of ParotitisVaginal DrynessReynaud'sSensory PolyneuropathyRenal tubular Acidosis (usually subclinical)InvestigationRheumatoid Factor?(RF) positive in nearly 100% of patientsANA?positive in 70%Anti-Ro?(SSA) Abs in 70% of patients with PSSAnti-La?(SSB) Abs 30% of patients with PSSSchirmer's test: filter paper near conjunctival sac to measure tear formationHistology focal lymphocytic infiltrationHypergammaglobulinaemia, Low C4ManagementArtificial saliva and tearsPilocarpine may stimulate saliva productionStill's disease in adults Bimodal age (15-25 yrs and 35-45. Featuresarthralgia↑↑ serum ferritinRash salmon-pink, maculopapularPyrexiatypically rises in the late afternoon/early evening in a daily pattern and accompanies a worsening of joint symptoms and rashlymphadenopathyrheumatoid factor (RF) and anti-nuclear antibody (ANA) negativeThe Yamaguchi criteria is the most widely used criteria and has a sensitivity of 93.5%.?ManagementNSAIDsshould be used first-line?to manage fever, joint pain and serositisthey should be trialled for at least a week before steroids are added.steroidsmay control symptoms but won't improve prognosisIf symptoms persist, the use of Methotrexate or Anti-TNF therapy can be consideredAnakinra "IL1 inhibitor" competitively inhibits IL-1 by binding to the IL-1 receptor Plasma levels correlate well with IL-1 in synovial fluid and presence of synovitis.??Rituximab is usually instigated in patients who fail to respond to anakinra.Relapsing polychondritisA multi-systemic condition episodes of inflammation of cartilage (Commonest Pinna ears, other parts (nose and joints).May be associated with autoimmune diseases (SLE and systemic vasculitis).?Features:?Ears Auricular chondritis/ Hearing loss/ VertigoNasal nasal chondritis → saddle-nose deformityRespiratory tract hoarseness, aphonia, wheezing, inspiratory stridorOcular Episcleritis, scleritis, iritis, and keratoconjunctivitis siccaJoints arthralgiaLess commonly Valvular regurgitation, cranial nerve palsies, peripheral neuropathies, renal dysfunctionDiagnosis:?Various scoring systems (clinical + pathological + radiological criteria)TreatmentInduce remission: steroidsMaintenance: azathioprine, methotrexate, cyclosporin, cyclophosphamideChronic fatigue syndromeDiagnosed after ≥ 4 months of disabling fatigue (Mental + Physical) function > 50% of the time in the absence of other disease which may explain symptoms↑↑ females , Better prognosis in childrenpast psychiatric history has not been risk factorFeatures includeFatigue is the central featureSleep problems (insomnia, hypersomnia, unrefreshing sleep, a disturbed sleep-wake cycle)muscle and/or joint painsHeadachespainful lymph nodes without enlargementSore throatcognitive dysfunction (difficulty thinking, ↓↓concentrate, ↓↓short-term memory, and difficulties with word-finding)physical or mental exertion makes symptoms worsegeneral malaise or 'flu-like' symptomsdizziness, nausea, palpitationsInvestigationlarge number of screening blood tests FBC, U&E, LFT, glucose, TFT, ESR, CRP, calcium, CK, ferritin(, coeliac screening and also urinalysisManagementCBT - very effective, number needed to treat = 2Graded Exercise Therapy - a formal supervised program, not advice to go to the gym'Pacing' organising activities to avoid tiringlow-dose amitriptyline may be useful for poor sleepreferral to a pain management clinic if pain is a predominant featureFibromyalgia widespread pain throughout the body + tender points at specific anatomical sites. The cause of fibromyalgia is unknown. ↑↑↑ 30-50 Ys Women (5Times)FeaturesChronic pain: at multiple site, sometimes 'pain all over' neck, elbow regions, and knees.lethargyCognitive impairment: 'fibro fog'Sleep disturbance, headaches, dizziness are commonDiagnosis Clinical Classification criteria 9 pairs of tender points on the body. (least 11/ 18 points diagnosis of fibromyalgia more likely)Management Often difficult and needs to be tailored to the individual patient psychosocial and multidisciplinary approach is helpful. explanationaerobic exercise Strongest evidence baseCBTMedication pregabalin, duloxetine, amitriptylinePolymyalgia rheumaticaPathophysiologyoverlaps with temporal arteritishistology Vasculitis with giant cells W 'skips' certain sections Muscle bed arteries affected most in Polymyalgia RheumaticFeatures> 60 years oldusually rapid onset (e.g. < 1 month)Aching, morning stiffness in proximal limb muscles (not weakness)also mild polyarthralgia, lethargy, Depression, low-grade fever, anorexia, night sweatsInvestigationsESR > 40 mm/hrCK and EMG normalTreatmentPrednisolone 15mg/od - dramatic response Myopathiessymmetrical muscle weakness (proximal > distal)common problems are rising from chair or getting out of bathsensation normal, reflexes normal, no fasciculationCausesInflammatory polymyositisInherited Duchenne/Becker muscular dystrophy, myotonic dystrophyEndocrine Cushing's, ThyrotoxicosisAlcoholAnti-synthetase syndrome diagnosis is (Proximal Myopathy + Mechanic Hands +/- Lung Symptoms) association W interstitial lung disease - particularly non-specific interstitial pneumonia or NSIP.Dermatomyositisan inflammatory disorder causing symmetrical, proximal muscle weakness + skin lesionsidiopathic or C.T disorders or?underlying malignancy?Screening for malignancy? following a diagnosis of dermatomyositis (typically ovarian, breast and lung cancer, (20-25%) ↑↑W ageEX: ?presentation with weakness of UL + macular rash over his back. He is a heavy smoker and his sodium is 121 mmol/l small cell lung cancer Polymyositis variant of the disease where skin manifestations are not prominentFeaturesSkin featuresPhotosensitiveMacular rash over back and shoulderGottron's papules roughened red papules over extensor surfaces of fingersNail fold capillary dilatationHeliotrope rash in the periorbital regionOther featuresproximal muscle weakness +/- tendernessRaynaud'sRespiratory muscle weaknessinterstitial lung disease Fibrosing alveolitis or organising pneumoniaDysphagia, DysphoniaInvestigations↑↑ CK EMGmuscle biopsyAntibodies Majority of patients (around 80%) ANA positiveHighly specific anti-Mi-2 antibodies, but are only seen in around 25% of patients"polymyositis" Subtypes anti-Jo-1 antibodies Not common in dermatomyositis ↑↑common in Polymyositis disease associated with (lung involvement + Raynaud's + fever)ManagementPrednisolonearound 30% of patients have antibodies to aminoacyl-tRNA synthetases (anti-synthetase antibodies), including:antibodies against histidine-tRNA ligase (Anti- Jo-1) (also with polymiocytis and moresensitive)antibodies to signal recognition particle (SRP)anti-Mi-2 antibodies Polymyositisinflammatory disorder causing symmetrical, proximal muscle weaknessthought to be a T-cell mediated cytotoxic process directed against muscle fibresmay be idiopathic or associated with connective tissue disorders OR malignancyDermatomyositis is a variant ( skin manifestations are prominent, for example a purple (heliotrope) rash on the cheeks and eyelidstypically affects middle-aged, female:male 3:1FeaturesProximal muscle weakness +/- Loss of mucle massRaynaud'sRespiratory muscle weaknessMajor risk factor for premature death The anti-Jo-1 antibody with up to 70% of patients having concurrent ILD 5-year survival (60 -80%)?Discuss?(2)Improveinterstitial lung disease fibrosing alveolitis or organising pneumoniadysphagia, dysphoniaInvestigations↑↑ CK↑↑ muscle enzymes (lactate dehydrogenase (LD), aldolase, AST and ALT) 85-95% EMGmuscle biopsyAnti-Jo-1 antibodies associated with lung involvement, Raynaud's and fever Mixed connective tissue disease (MCTD, Sharp's syndrome)Heterogeneous, multi-system autoimmune disorder. It is a distinct clinical entity, butfeatures of ((SLE) + Systemic Sclerosis (SSc) + Myositis may all be present. It is associated with anti-U1 ribonucleoprotein (RNP) antibodies (not completely specific and may also be seen in definite SSc and SLE) DD. 'undifferentiated connective tissue disease'. features of ≥ 1'classical' C.T disease, but do not meet diagnostic criteria. Anti-U1 RNP is absentEpidemiologyMale:female ratio 1:3 30-40 Ys may present in childrenPresentation:Raynaud's phenomenon often precedes other symptoms and occurs in 90% of casesPolyarthralgia/arthritisMyalgia'Sausage fingers'(dactylitis)Other clinically important features:Dermatological photosensitive rash, scleroderma-like changes, alopeciaGIT Oesophageal dysfunctionRespiratory pleuritis, pulmonary hypertension, interstitial lung diseaseHaematological anaemia, lymphadenopathy, splenomegaly, rarely TTPCVS pericarditis, pericardial effusion, accelerated coronary artery diseaseRenal glomerulonephritis (tends to be milder than SLE)CNS : seizures, mood disturbanceInvestigations:Exclude other connective tissue disease/vasculitisBloods FBC anaemia, leucopenia, thrombocytopeniaU+E: renal impairment, CRP/ESR raisedANA (usually) positive, anti Ds-DNA and scleroderma-specific antibodies (e.g. Anti-Scl70) are negativeAnti-U1 RNP (an extractable nuclear antigen, ENA), must be positiveOrgan-specific investigations, ECG, echo, CT chest, MRI brainManagement:No large-scale trials - patients have been included in trials for SLE/SSc and show similar levels of response to immunosuppression/DMARDsCalcium channel blockers may be used for the treatment of Raynaud'sProton pump inhibitors for reflux diseaseEndothelin receptor antagonists/prostacyclin analogues in pulmonary hypertensionSmoking cessation, moderate exercisePrognosis:1/3 long-term remission, 1/3 have chronic symptoms, 1/3 develop severe systemic involvement and premature death.Systemic sclerosisUnknown aetiology characterised by hardened, sclerotic skin and other connective tissues. It is ↑↑ 4* 1 females.There are three patterns of disease:Limited cutaneous systemic sclerosisDiffuse cutaneous systemic sclerosisScleroderma (without internal organRaynaud's "first sign"Scleroderma face and?distal limbs?predominatelyanti-Centromere antibodiesCREST syndrome a subtype of limited systemic sclerosisCalcinosis, Raynaud's phenomenon, oEsophageal dysmotility, Sclerodactyly, TelangiectasiaMalabsorption can develop in these patients secondary to bacterial overgrowth of the sclerosed small intestinePHT one of the more common late complications Scleroderma trunk and proximal limbs predominatelyscl-70 antibodiesCommonest cause of death respiratory involvement,(80%)?interstitial lung disease (ILD) and PAHOther complications renal disease and HTNPoor prognosistightening and fibrosis of skinmay be manifest as plaques (morphoea) or linearAntibodiesANA positive in 90%RF positive in 30%anti-scl-70 antibodies associated with diffuse cutaneous systemic sclerosisanti-centromere antibodies associated with limited cutaneous systemic sclerosisBehcet's syndrome Multisystem disorder with presumed autoimmune-mediated inflammation of the arteries and veins. Triad (oral ulcers + genital ulcers + anterior uveitis)Epidemiologymore common in the eastern Mediterranean (Turkey)More common and severe in men 20 - 40 years old ) (complicated gender distribution which varies according to country. associated with HLA B5130% of patients have a positive family historyFeatures1) oral ulcers 2) genital ulcers 3) anterior uveitis not Conjunctivitis Ocular involvement is the most feared complication?Conjunctivitis is rare and is much less common than anterior uveitis. Others (Retinal vasculitis, Iridocyclitis and Chorioretinitis)Thrombophlebitis and deep vein thrombosisarthritisneurological involvement (aseptic meningitis)GI abdo pain, diarrhoea, colitisErythema nodosumDiagnosisno definitive testdiagnosis based on clinical findings+Ve pathergy test?is suggestive (puncture site following needle prick becomes inflamed with small pustule forming)*more specifically HLA B51, a split antigen of HLA B5McArdle's diseaseAR type V glycogen storage disease caused by Myophosphorylase deficiency ↓↓ muscle glycogenolysisFeaturesmuscle pain and stiffness following exercise 'second-wind' phenomenon and present Muscle cramps Distal muscle Myoglobinuria Dark Urine after exerciselow lactate levels during exerciseDD. Polymyositis and dermatomyositis cause a more marked ↑↑↑ CK which can be up to 100 times the upper limit of normal.Polyarteritis nodosaVasculitis of medium-sized arteries with necrotizing inflammation leading to aneurysm formation. ↑↑middle-aged men, Associated with?hepatitis B.FeaturesFever, malaise, arthralgiaWeight lossHypertensionMononeuritis multiplex sensorimotor polyneuropathy (Pt Ulner palsy radial facial new foot drop or wrist drop ….)Testicular painlivedo reticularisHaematuria, renal failurePerinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with 'classic' PANhepatitis B serology +Ve 30% of patientsDiagnosisNo ↑↑ correlated Abs is likely to be positiveConfirmed Diagnosis Biopsy showing necrotizing arteritisEscaped lesions disease is focal (biopsy should target sites suggested by clinical evaluation)Samples of subcutaneous tissue, sural nerve, and muscle are preferred to samples from the kidneys or liver; kidney and liver biopsies Might be falsely negative and may cause bleeding from unsuspected microaneurysms.Arteriography Typical aneurysms in medium-sized arteries. MRA may show microaneurysms, but some abnormalities may be too small for it to detect.Labs ↑↑ (ESR, Platlet & TLC up to 20,000 to 40,000/L)Anaemia caused by blood loss or renal failureproteinuria, and microscopic haematuria are the most common abnormalities. Liver low serum albumin AST and ALT are often mildly elevated. Testing for hepatitis B and C should be done.Temporal arteritis large vessel vasculitis (polymyalgia rheumatic) PMR Histology shows changes which characteristically 'skips' certain affected artery whilst damaging others.Featurestypically patient > 60 years oldusually rapid onset (< 1 month)Headache (found in 85%)Jaw claudication (65%) very specific sign for temporal arteritis.Visual disturbances secondary to anterior ischemic optic neuropathytender, palpable temporal arteryAround 50% have PMR Aching, Morning stiffness in proximal limb muscles (not weakness)lethargy, depression, low-grade fever, anorexia, night sweatsCriteria requires 3 of the following for GCA diagnosis:1. Age > 50 y/o2. New onset localised headache3. Temporal artery tenderness or ↓↓pulsation4. ESR > 50mm/hr5. Temporal artery biopsy positiveInvestigations↑↑ ESR > 50 mm/hr (note ESR < 30 in 10% of patients). CRP may also be elevatedTemporal artery biopsy skip lesions may be present–Ve Temporal artery biopsy can occur in up to 50 % of patientsnote creatine kinase and EMG normalTreatmentUncomplicated GCA (no visual involvement and/or jaw/tongue claudication) Oral prednisolone 40-60mg daily until symptoms and investigations plicated GCA (visual involvement and/or jaw/tongue claudication)IV Methylprednisolone 500-1000mg for 3 days before starting oral prednisolone.Urgent ophthalmology review visual symptoms should be seen the same-day by an ophthalmologist. Visual damage is often irreversibleLong term therapylong-term steroid + Bone sparing agents (a bisphosphonate and vitamin D) + Gastroprotective drug (e.g omeprazole). Low dose aspirin ↓↓ rate of visual loss and cerebrovascular accidents in GCA.ANCA There are two main types of anti-neutrophil cytoplasmic antibodies (ANCA) - cytoplasmic (cANCA) and perinuclear (pANCA) For the exam, remember:cANCA - granulomatosis with polyangiitis (Wegener's granulomatosis)pANCA - Churg-Strauss syndrome + others (see below)cANCAmost common target serine proteinase 3 (PR3)some correlation between cANCA levels and disease activitygranulomatosis with polyangiitis, positive in > 90%microscopic polyangiitis, positive in 40%pANCAtarget myeloperoxidase ( most common) neutrophil protein whose primary role is the generation of oxygen free radicals. (MPO)other targets include lysosome, cathepsin G and elastasecannot use level of pANCA to monitor disease activityassociated withimmune crescentic glomerulonephritis (positive in c. 80% of patients)microscopic polyangiitis, positive in 50-75%Churg-Strauss syndrome, positive in 60%primary sclerosing cholangitis, positive in 60-80%granulomatosis with polyangiitis, positive in 25%Other causes of positive ANCA (usually pANCA)IBD (UC > Crohn's)C.T disorders: RA, SLE, Sjogren'sautoimmune hepatitisTesting for ANCA Enzyme-linked immunosorbent assay (ELISA) or immunofluorescence. The former detects anti-MPO or anti PR3 antibodies in the blood. Immunostaining would show different patterns depending on the conditionMarfan's syndrome AD C.T disorder defect in the FBN1 gene on chromosome 15 that codes for the?protein fibrillin-1A Glycoprotein structure wraps around elastin. It affects (1 in 3,000) people.FeaturesTall stature with Arm span to height ratio > 1.05high-arched palateArachnodactylypectus excavatumpes planusscoliosis of > 20 degreesHEART ?Dilation of the aortic sinuses?(90%) aortic aneurysm, aortic dissection, aortic regurgitation,?mitral valve prolapse?(75%),Lungs ?Repeated pneumothoracesEyes upwards lens dislocation?(50%) (superotemporal ectopia lentis),?blue sclera, myopia, Glucoma, Retinal dislocation. CNS Dural ectasia?(ballooning of the dural sac at the lumbosacral level) lower back pain associated with neurological problems such as bladder and bowel dysfunctionThe life expectancy of patients used to be around 40-50 years. With the advent of regular echocardiography monitoring and beta-blocker/ACE-inhibitor therapy this has improved significantly over recent years. Aortic dissection and other CVS problems remain the leading cause of death however.Inferonasal ectopia lentis is characteristic of homocystinuriaPseudoxanthoma elasticum AR(AD in minority) Abnormality in elastic fibres FeaturesEarliest sign "Skin Changes" 'plucked chicken skin' appearance (small yellow papules on the neck, antecubital fossa and axilla)Retinal Angioid streaks small breaks in Bruch's membrane ( Elastic tissue containing membrane of the retina) CVS MV prolapse, ↑↑↑ IHDGIT Hge*there are reports of autosomal dominant inheritance in a minority of casesEhler-Danlos syndrome AD C.T disorder that mostly affects type III collagen. tissue being more elastic than normal joint hypermobility and increased elasticity of the skin.Features and complicationsElastic, fragile skin Bruises joint hypermobility: recurrent joint dislocationAR , MV prolapse and aortic dissectionSubarachnoid HgeAngioid retinal streaksDDCollagen type I Osteogenesis imperfectaCollagen type IIIEhler DanlosCollagen type IVGoodpostureCollagen type V Less common Ehler DanlosGoutMicrocrystal synovitis (deposition of monosodium urate monohydrate in the synovium). predominantly in the superficial portions of the articular cartilage Chronic hyperuricaemia (uric acid > 0.45 mmol/l)Decreased excretion of uric acidChronic kidney disease ↓↓renal excretion (90%) 1ry gout. 2ry risk factors such as alcohol intake and medications should also be investigatedDrugsDiuretics Thiazides, Furosemide, IndipamideCiclosporinAlcoholCytotoxic agentsPyrazinamideAspirin balanced against the cardiovascular benefits of aspirin and the study showed patients coprescribed allopurinol were not at an increased riskLead toxicityIncreased production of uric acidMyeloproliferative/lymphoproliferative disorderCytotoxic drugsSevere psoriasisLesch-Nyhan syndromehypoxanthine-guanine phosphoribosyl transferase (HGPRTase) deficiencyX-linked recessive only seen in boysGout, Renal failure, Neurological deficits, Learning difficulties, Self-mutilationFeaturesEpisodes days maximal intensity with 12 hs , often symptom-free between episodes. The main Pain: this is often very significant 1st metatarsophalangeal (MTP) joint (70%) (ankle, wrise, knee)SwellingErythemaInvestigations XR, CT, MRI and bone scintigraphy helpful diagnostic clues inability to assess early soft tissue changes. not seen radiographically until 6-12 yrs after the initial acute attack. Radiological features of gout include:Joint effusion is an early signThe most characteristic lesion "Double-contour sign" Hyperechoic, irregular band over the superficial margin of the joint cartilage" produced by deposition of monosodium urate crystals on the surface of the hyaline cartilage, ↑↑interface of the cartilage surface, reaching a thickness similar to the subchondral bone.?Well-defined 'punched-out' erosions + Sclerotic margins ina juxta-articular distribution, often with overhanging edgesRelative preservation of joint space until late diseaseEccentric erosionsPeriarticular osteopenia (in contrast to rheumatoid arthritis)Soft tissue Tophi (Roentgenography) may be seenThe most reliable method Needle aspiration Monosodium urate crystals. Acute management1st Line NSAIDs or?Colchicine?Maximum dose of NSAID prescribed until 1-2 days after the symptoms have settled. Gastroprotection (e.g. a proton pump inhibitor) may also be indicatedColchicine(- -) microtubule polymerization by binding to tubulin, interfering with mitosis. Also (- -) Neutrophil motility and activitySlower onset of action. The main S/E?diarrheaCKD ↓↓ dose or ↑↑ the dosage interval if eGFR 10-50ml/minute/1.73m?; Avoid if eGFR < 10mL/minute/1.73m?.2nd Line Oral steroids?NSAIDs and colchicine are contraindicatedprednisolone 15mg/day is usually usedintra-articular steroid injectionif the patient is already taking allopurinol it should be continuedUrate-lowering therapy (ULT)All patients after their?first attack of gout, ULT is?particularly?recommended if:≥ 2 attacks in 12 monthsTophiRenal diseaseUric acid renal stonesProphylaxis if cytotoxics or diuretics1st Line Allopurinol Should not be started until 2 weeks after an acute attack, as starting too early may precipitate a further attack.Better for a patient to make long-term drug decisions whilst not in painInitial dose of 100 mg/ Day ↑↑every few weeks (aim serum uric acid of < 300 ?mol/l.)Lower initial doses reduced eGFRColchicines cover? starting allopurinol.?NSAIDs?can be used if colchicine cannot be tolerated. may need to be continued for 6 months2nd-line Febuxostat (Xanthine Oxidase inhibitor)in refractory cases other agents may be tried:Uricase (Urate Oxidase) enzyme catalyzes conversion of urate to the degradation product allantoin (in certain mammals but not humaPegloticasePolyethylene glycol modified mammalian uricaseUsed in persistent symptomatic and severe gout despite the adequate use of urate-lowering therapy.Achieve rapid control of hyperuricemia. It is given as an infusion once/ 2 weeksLifestyle modificationsreduce alcohol intake and avoid during an acute attacklose weight if obeseavoid food high in purines (Liver, kidneys, seafood, oily fish (mackerel, sardines) and yeast products)Other pointsstopping precipitating drugs (thiazides)losartan has a specific uricosuric action coexistent hypertension↑↑ vitamin C intake (either supplements or through normal diet) may also ↓↓serum uric acid levelsPseudogout Microcrystal synovitis caused by the?deposition of Ca++ pyrophosphate dihydrate crystals in the synovium. Risk factors↑↑PTH Hyperparathyroidism↑↑ (Fe ++ ) Haemochromatosis↑↑ (Copper) Wilson's disease↑↑ (GH) Acromegaly↓↓ (Mg, P+)Featuresknee, wrist and shoulders most commonly affectedjoint aspiration:?weakly-positively Birefringent rhomboid-shaped crystals↑↑ Transferrin Saturation (confirm Haemochromatosis) X-RayNon-specific changes such as loss of joint space?Chondrocalcinosis in the knee linear calcifications of the meniscus and articular cartilage (DD. pseudogout from gout)ManagementAspiration of joint fluid exclude septic arthritisNSAIDs or intra-articular, intra-muscular or oral steroids as for goutLangerhans cell histiocytosisA rare condition associated with the abnormal proliferation of histiocytes formation of multiple granulomas. It presents in childhood with bony lesions.FeaturesBone pain, typically in the skull or proximal femurRecurrent otitis media/MastoiditisCutaneous nodulesproliferative condition of the dendritic cells in the skinSkin Biopsy Tennis racket-shaped Birbeck granules on electromicroscopyPaget's disease of the bone"Osteitis deformans" ↑uncontrolled bone turnover. disorder of Osteoclasts, ↑↑ osteoclastic resorption followed by ↑↑ osteoblastic activity. It is common (UK prevalence 5%) but symptomatic(1 in 20) patients.↑↑↑ skull, spine/pelvis, and long bones of the lower extremities Predisposing factorsincreasing agemale sexnorthern latitudefamily historyClinical features - only 5% of patients are symptomatictypically ?older male + bone pain + isolated ↑↑ ALPbone pain (pelvis, lumbar spine, femur)classical, untreated features bowing of tibia, bossing of skullcalcium* and phosphate are typically normal (↑↑ prolonged immobilization)other markers of bone turnover includepro-collagen type I N-terminal propeptide (PINP), serum C-telopeptide (CTx), urinary N-telopeptide (NTx)↑↑ Blood & urinary HydroxyprolineX-ray: Skull thickened vault, osteoporosis circumscriptaOsteolytic lesions + patch sclerosisIndications for treatment bone pain skull or long bone deformity Fracture periarticular Paget'sBisphosphonate?(either oral risedronate or IV zoledronate) + Ca and Vit D.Calcitonin is less commonly used nowComplicationsdeafness (cranial nerve entrapment)bone sarcoma (1% if affected for > 10 years)fracturesskull thickeninghigh-output cardiac failureOsteoarthritis (OA) The trapeziometacarpal joint (base of thumb) is the most common site of hand osteoarthritis.Managementall offered (weight loss, local muscle strengthening exercises and general aerobic fitness).first-line analgesics paracetamol and topical NSAIDs are. Topical NSAIDs (OA of the knee or hand)2nd-line treatment oral NSAIDs/COX-2 inhibitors, opioids, capsaicin cream and intra-articular corticosteroids. A proton pump inhibitor should be co-prescribed with NSAIDs and COX-2 inhibitors. These drugs should be avoided if the patient takes aspirinnon-pharmacological treatment options include supports and braces, TENS and shock absorbing insoles or shoesif conservative methods fail then refer for consideration of joint replacementWhat is the role of glucosamine?normal constituent of glycosaminoglycans in cartilage and synovial fluidSignificant short-term symptomatic benefits including significantly ↓↓ joint space narrowing and improved pain scoresOsteomalaciaNormal bony tissue but ↓↓mineral contentRickets if when growing Osteomalacia if after epiphysis fusionTypesVit D deficiency e.g. malabsorption, lack of sunlight, dietRenal failureDrug anticonvulsantsVit D resistant inheritedliver disease CirrhosisFeaturesRickets knock-knee, bow leg, features of hypocalcaemiaOsteomalacia bone pain, fractures, muscle tenderness, proximal myopathyInvestigation↓↓ 25(OH) vitamin D (in 100% of patients, by definition)↑↑ ALP (95-100%)↓↓ (Ca++, P) (in around 30%)X-RayChildren Cupped, Ragged Metaphysical surfacesAdults Translucent Bands (Looser's zones OR Pseudo fractures)TreatmentCa with vitamin D tabletsDD. Osteoporosis blood values are normal ? 1ry hyperparathyroidism ('Refer for a technetium-MIBI subtraction scan') are associated with↑↑Ca++Vitamin D supplementationPatients with osteoporosis should always be given calcium/vitamin D supplements so testing is not considered necessary. People who are at higher risk of vitamin D deficiency should be treated anyway so again testing is not necessary.all?pregnant?and breastfeeding women should take a daily supplement containing 10?g of vitamin Dall children aged (6 months - 5 years). Babies fed with formula milk do not need if they are taking > 500ml of milk (fortified with vitamin D)Adults > 65 years'people who are not exposed to much sun should also take a daily supplement' (housebound patients) Testing for vitamin D deficiency Testing may be appropriate in the following situtations:patients with bone diseases may be improved with vitamin D (known osteomalacia or Paget's disease)patients with bone diseases, prior to specific treatment where correcting vitamin deficiency is appropriate (IV zolendronate or denosumabpatients with musculoskeletal symptoms could be attributed to vitamin D deficiency ( bone pain ?osteomalaci)Measurement of serum 25-OH vitamin D is the best way of estimating vitamin D status.< 30 nmol/l Deficiency treatment recommended30-50 nmol/l Insufficiency treatment for patients with fragility fracture, Osteoporosis.symptoms suggestive of vitamin D deficiency,↓↓ exposure to sunlight, ↑↑ PTH, conditions associated with malabsorption50- 75 nmol/l Adequate reassurance and advice on maintaining adequate vitamin D ( safe sunlight exposure and diet) Treatment Load with vitamin D and then continue on maintenance. In patients with good calcium intake and normal serum calcium, giving oral calcium may actually be detrimental. This is due to adverse CVS outcomes (↑↑ tissue and vascular calcification CI IHDOsteopetrosis"Marble Bone Disease" rare disorder of Defective osteoclast function failure of normal bone resorption dense, thick bones prone to fractureBone pains and neuropathies are common.Ca++, P+ & ALP are normalTreatment Stem cell transplant and interferon-gamma.OsteoporosisAdvancing age and female sex are significant risk factors for osteoporosis. Prevalence (2% at 50 ys) & > 25% at 80 yrisk factors and 2ry causes the most 'important' ones (major risk assessment tools )such as FRAX:history of?glucocorticoid?userheumatoid arthritisalcohol excesshistory of parental hip fracture↓↓ BMIcurrent smokingOther risk factorsSedentary lifestylepremature menopauseCaucasians and AsiansEndocrine DM, hyperthyroidism, hyperparathyroidism, ↓↓↓GH, Hypogonadism (Turner's,?Testosterone deficiency)Multiple myeloma, LymphomaGIT disorders:?IBD, Malabsorption (Coeliac's), Gastrectomy, Liver diseaseChronic kidney diseaseOsteogenesis imperfecta, HomocystinuriaMedications that may worsen osteoporosis (other than glucocorticoids):SSRIsAntiepilepticProton pump inhibitorsGlitazonesLong term heparin therapyAromatase inhibitors e.g. AnastrozoleInvestigations for secondary causesIf a patient is diagnosed with osteoporosis or has a fragility fracture testing for the following reasons:exclude diseases that mimic osteoporosis (osteomalacia, myeloma);identify the cause of osteoporosis and contributory factors;assess the risk of subsequent fractures;select the most appropriate form of treatmentThe following investigations are recommended by NOGG:History and physical examinationCB, ESR or CRP, Serum Ca++Albumin, Creatinine, phosphate, ALPand liver transaminasesThyroid function testsBone densitometry ( DXA)Other procedures, if indicatedLateral radiographs of lumbar and thoracic spine/DXA-based vertebral imagingProtein immunoelectrophoresis and urinary Bence-Jones proteins25OHDPTHSerum testosterone, SHBG sex hormone binding globulin, FSH, LH (much likely in a middle-aged male)Serum prolactin24 hour urinary cortisol/dexamethasone suppression testEndomysial and/or tissue transglutaminase antibodies (coeliac disease)Isotope bone scanMarkers of bone turnover, when availableUrinary calcium excretionSo from the first list we should order the following bloods as a minimum for all patients:full blood counturea and electrolytesliver function testsbone profileCRPthyroid function testsDEXA scanT score means the number of SDs above or below the mean for a healthy 30Ys adult of the same sex and ethnicity as the patient T score (-1) bone mass of one standard deviation < that of young reference population.-1.0 = normal-1.0 to -2.5 = osteopaenia< -2.5 = osteoporosisZ score comparing the patients bone density to individuals of a /similar age /gender and ethnic factorsDiagnosing of 2ry osteoporosis used for children, young adults, pre-menopausal women and men < 50 YsAbnormal Z-scores confirm a diagnosis of 2ry osteoporosis.?ManagementTreatment is indicated following Osteoporotic fragility fractures in postmenopausal women confirmed to have osteoporosis (a T-score of - 2.5 SD or below). In women ≥ 75 years, a DEXA scan may not be required 'if clinically inappropriate or unfeasible'vitamin D and calcium all women unless the clinician is confident they have adequate calcium intake and are vitamin D repleteAlendronate is first-line25% of patients cannot tolerate alendronate, (upper GIT problems) Risedronate OR Etidronate (see treatment criteria below)Strontium Ranelate and Raloxifene if patients cannot tolerate bisphosphonates (see treatment criteria below)Treatment criteria for patients not taking alendronateAge, T-score and risk factors:Parental history of hip fractureAlcohol intake ≥ 4 units per dayRheumatoid arthritisT-score criteria for Risedronate or Etidronate < others ( So, 2nd line drugs)If Alendronate, Risedronate or Etidronate cannot be taken Strontium ranelate or Raloxifene (based on strict T-scores (60Y T-score < -3.5)The strictest criteria are for DenosumabSupplementary notes on treatmentBisphosphonatesAnalogues of pyrophosphate ((- -) osteoclasts? by ↓↓ recruitment and ↑↑ apoptosis ↓↓ demineralisation in bone alendronate, risedronate and etidronate prevention and treatment of post-menopausal and glucocorticoid-induced osteoporosisall three shown to ↓↓ risk of both vertebral and non-vertebral fractures Alendronate, Risedronate may be superior to Etidronate in preventing hip fracturesIbandronate once-monthly oral bisphosphonateZoledronic Acid is another type of bisphosphonate. It attaches to bone cells and ↓↓ rate of bone change.Treatment of osteoporosis & fracture prevention in cancer such as multiple myeloma and prostate cancer.Clinical usesPrevention and treatment of osteoporosisHypercalcaemiaPaget's diseasepain from bone metatasesAdverse effectsOesophageal reactions oesophagitis, oesophageal ulcers (especially alendronate)Osteonecrosis of the jaw↑↑ risk of?atypical stress fractures?of the proximal femoral shaft in patients taking alendronateacute phase response: fever, myalgia and arthralgia may occur following administrationHypocalcaemia: ↓↓calcium efflux from bone. Usually clinically unimportant Precautions with oral bisphosphonates'Tablets should be swallowed whole with plenty of water while sitting or standing; to be given on an empty stomach at least 30 minutes before breakfast (or another oral medication); patient should stand or sit upright for at least 30 minutes after taking tablet'Hypocalcemia/vitamin D deficiency should be corrected before giving bisphosphonates. when starting bisphosphonate treatment for osteoporosis,?calcium should only be prescribed if dietary intake is inadequate.Vitamin D supplements are normally given.The duration of bisphosphonate according to the level of risk. at 5 years if the following apply:Patient is < 75-years-oldFemoral neck T-score of > -2.5low risk according to FRAX/NOGGAlendronate first-line treatment Not tolerated then (Risedronate or Etidronate). Following this the advice becomes more complicated with the next-line medicationsVitamin D and calcium↓↓ fracture rates in the general population at risk of osteoporotic fractures - may reduce rates in frail, housebound patientsRaloxifene - selective oestrogen receptor modulator (SERM)Prevent bone loss and to ↓↓ risk of vertebral fractures, NOT ↓↓ risk of non-vertebral fractures↑↑ bone density in the spine and proximal femurmay worsen menopausal symptoms↑↑ risk of thromboembolic events↓↓ risk of breast cancerStrontium ranelate?'Dual action bone agent' ↑↑deposition of new bone by osteoblasts (++ differentiation of pre-osteoblast to osteoblast) and ↓↓ resorption of bone by↓osteoclasts↑↑ Safety concerns only be prescribed by a specialist in secondary careOnly when other treatments for osteoporosis↑↑ CVS History of CVS ↑↑ thromboembolic events it is not used in patients with a history of venous thromboembolismmay cause serious skin reactions such as Stevens Johnson syndromeDenosumabHuman monoclonal antibody inhibits RANK Ligand, (- -) maturation of osteoclastsDose single S.C injection/ 6 monthsLarger dose (120mg) /1 month prevention of skeletal-related events (Pathological fractures)?(bone metastases from solid tumours. Effective and well toleratedIndication only if certain T score and other risk factor criteria being met. Side-effects Dyspnoea and diarrhoea "two most common 1 in 10 patients"|.↓ Ca++?and URTI. Cases of?atypical femoral fractures?(look out for patients complaining of unusual thigh, hip or groin pain.Teriparatiderecombinant form of PTHvery effective ↑↑bone mineral density but role in the management of osteoporosis yet to be clearly definedHormone replacement therapy↓↓ incidence of vertebral fracture and non-vertebral fracturesONLY if vasomotor symptoms (Risk CVS and breast cancer)Hip protectors↓↓hip fractures in nursing home patients compliance is a problemFalls risk assessmentno evidence to ↓↓fracture rateshowever, ↓↓ rate of falls and should be considered in management of high risk patientsGlucocorticoid-induced ↑↑↑ risk if dose = prednisolone 7.5mg a day for ≥ 3 Ms. manage patients in an anticipatory (steroids for at least 3 months + start bone protection straight) until 3 months has elapsed.Patient with newly diagnosed polymyalgia rheumatica prednisolone > 3 months bone protection should be commencedManagement of patients at risk of corticosteroid-induced osteoporosis> 65 years OR previous fragility fracture bone protection.?< 65 years bone density scanT scoreManagement > 0ReassureBetween 0 and -1.5Repeat in 1-3 years < -1.5Offer bone protectionTreatment Alendronate + calcium + vitamin D replete.Osteogenesis imperfect"Brittle bone disease" AD abnormality in type 1 collagen?due to ↓↓ synthesis of pro-alpha 1 or pro-alpha 2 collagen polypeptides bone fragility and fractures. The most common, and milder, form is type 1. Featurespresents in childhoodfractures following minor traumablue scleradeafness secondary to otosclerosisdental imperfections are commonInvestigationsadjusted calcium, phosphate, parathyroid hormone and ALP results are usually normal?in osteogenesis imperfectaAnkylosing spondylitisHLA-B27 associated spondyloarthropathy. Young man sex ratio 3:1 aged 20-30 years presents with lower back pain and stiffness of insidious onsetstiffness is usually worse in the morning and improves with exercisethe patient may experience pain at night which improves on getting upClinical examination↓↓ (lateral flexion & forward flexion) ?loss of lumbar lordosis Schober's test - a line is drawn 10 cm above and 5 cm below the back dimples (dimples of Venus). The distance between the two lines ↑↑ by > 5 cm when the patient bends as far forward as possible↓↓ chest expansion, ↑↑ thoracic kyphosisOther features -?the 'A's?Anterior UveitisApical FibrosisARAV node blockAmyloidosisCauda Equina syndromeAchilles tendonitisPeripheral Arthritis (25%, more common if female)InvestigationsBLOOD↑↑ (ESR, CRP) although normal levels do not exclude ankylosing spondylitis.HLA-B27 is of little use in making the diagnosis as it is positive in:90% of patients with ankylosing spondylitis10% of normal patientsBACKPlain x-ray of the sacroiliac joints is the most useful investigation in establishing the diagnosis. Radiographs may be normal early in disease, later changes include:Sacroiliitis Subchondral erosions, Sclerosissquaring of lumbar vertebrae'bamboo spine'?(late & uncommon) Complete fusion of anterior and posterior elements??Dagger sign ?bamboo spine with a single central radiodense line related to ossification of supraspinous and interspinous ligamentssyndesmophytes: due to ossification of outer fibers of annulus fibrosusIf the x-ray is negative for sacroiliac joint involvement in ankylosing spondylitis but suspicion for AS remains high, MRI Signs of early inflammation involving sacroiliac joints (bone marrow oedema) confirm the diagnosis of AS and prompt further treatment.?Chestx-ray?apical fibrosisSpirometry may show a restrictive defect due to a combination (pulmonary fibrosis + kyphosis + Ankylosis) of the costovertebral joints.Managementencourage regular?exercise?such as swimmingNSAIDs are the first-line treatmentphysiotherapyDisease-modifying drugs used to treat rheumatoid arthritis (sulphasalazine) only really useful if there is peripheral joint involvementAnti-TNF therapy? Persistently ↑↑↑disease activity despite conventional treatments'Etanercept and Adalimumab should be used earlier in the course of the disease (Under trial)It improves Quality of life, Spinal mobility, Extra-articular features, Early morning stiffness. It does not affect Radiological progressionLower back pain: common presentations with non-specific muscular nature, but there are some possible causes which may need specific treatment.?Red flags for lower back painage < 20 years or > 50 yearssystemically unwell e.g. weight loss, feverhistory of previous malignancyhistory of traumaNight painFacet jointacute or chronicPain worse in the morning and on standingOn examination pain over the facets. The pain is typically worse on extension of the backSpinal stenosisUsually gradual onsetUnilateral or bilateral 'aching', 'crawling' leg pain ± back pain, numbness, and weakness is worse on walking. ↓↓ sitting down, leaning forwards and crouching downClinical examination is often normalRequires MRI to confirm diagnosis ?narrowing of the spinal canalAnkylosing spondylitisTypically a young man with lower back pain and stiffnessStiffness is usually worse in morning and improves with activityPeripheral arthritis (25%, more common if female)Peripheral arterial diseasePain on walking, relieved by restAbsent or weak foot pulses and other signs of limb ischaemiaPast history may include smoking and other vascular diseasesprolapsed lumbar disc usually produces clear?dermatomal leg pain?associated with neurological deficits.Featuresunilateral leg pain usually worse than back (Back Pain LL)pain often worse when sitting DD. Spinal stenosisSite of compressionFeaturesL3 nerve root compressionSensory loss over anterior thighWeak quadriceps↓↓ knee reflexPositive femoral stretch testL4 nerve root compressionSensory loss anterior aspect of kneeWeak quadriceps↓↓ knee reflexPositive femoral stretch testL5 nerve root compressionSensory loss dorsum of footWeakness in foot and big toe dorsiflexionReflexes intactPositive sciatic nerve stretch testS1 nerve root compressionSensory loss posterolateral aspect of leg and lateral aspect of footWeakness in plantar flexion of foot↓↓ ankle reflexPositive sciatic nerve stretch testManagementsimilar to that of other musculoskeletal lower back pain: analgesia, physiotherapy, exercisesif symptoms persist (after 4-6 weeks) then referral for consideration of MRI is appropriateiliopsoas abscessA collection of pus in iliopsoas compartment (iliopsoas and iliacus).Primary (Mortality 2.4%)Haematogenous spread of bacteriaStaphylococcus aureus: most commonSecondary (Mortality up to 19-20%)Crohn's (commonest cause in this category)Diverticulitis, colorectal cancerUTI, GU cancersVertebral osteomyelitisFemoral catheter, lithotripsyEndocarditisClinical featuresFever/back pain with pain on extension of the hip → iliopsoas abscess (Not resolver by Antibiotics)FeverBack/flank painLimpWeight lossClinical examinationPatient in the supine position with the knee flexed and the hip mildly externally rotatedSpecific tests to diagnose iliopsoas inflammation:Place hand proximal to the patient's ipsilateral knee and ask patient to lift thigh against your hand pain due to contraction of Psoas muscle.Lie the patient on the normal side and?hyperextend the affected hip pain as the psoas muscle is stretched.InvestigationCT is the gold standardManagementAntibioticsPercutaneous drainage? successful in around 90% of casesSurgery is indicated if:1. Failure of percutaneous drainage2. Presence of an another intra-abdominal pathology which requires surgerySeptic arthritismost common organism ?Staphylococcus auras, young adults sexually active?Neisseria Gonorrhoeae?should also be considered↑↑ in?kneeThe?Kocher criteria?for the diagnosis of septic arthritis:fever >38.5 degrees CNon-weight bearing↑↑ ESR↑↑ WCCThe three classic differentials for this presentation Septic arthritis, Gout and Pseudogout Culture will enable a positive diagnosis of septic arthritis,microscopy and gross appearance the diagnosis of crystal arthropathy.?Managementsynovial fluid should be obtained before starting treatmentIV antibiotics cover Gram-positive cocci are indicated (?flucloxacillin?or clindamycin if penicillin allergic) (6-12 weeks)Needle aspiration should be used to decompress the joint (Even w ↑↑ INR)arthroscopic lavage may be requiredReactive arthritisFollowing infection (organism not recovered from joint). Post-STI (Chlamydia Trachomatis) "Acquired reactive arthritis" SARA) OR GIT "Salmonella"One of the HLA-B27 associated seronegative spondyloarthropathies. It encompasses Reiter's syndrome (urethritis, conjunctivitis and arthritis) following a dysenteric EpidemiologyPost-STI men > Females (10:1)Post-dysenteric form equal sex incidenceFeatureswithin 4 weeks of initial infection lasts around 4-6 monthsArthritis Asymmetrical Oligoarthritis of lower limbs, DactylitisUrethritisEye Conjunctivitis (10-30%), anterior uveitisSkin Circinate balanitis (Painless vesicles on the coronal margin of the Prepuce)keratoderma Blenorrhagica (Waxy yellow/brown papules on palms and soles)25% of patients recurrent episodes, 10% of patients chronic disease:Post-dysenteric formPost-STI formShigella?flexneriSalmonella?typhimuriumSalmonella?enteritidisYersinia enterocoliticaCampylobacterChlamydia?trachomatisManagementSymptomatic: analgesia, NSAIDS, intra-articular steroidsSulfasalazine & Methotrexate are sometimes used for persistent diseasesymptoms rarely last > 12 monthsOsteomyelitis Infection of bone Staph. aureus?is the most common cause except in patients with sickle-cell anaemia and hemoglobinopathies ?Salmonella??(usually preceded by GIT upset. Predisposing conditionsD.MSickle cell anaemiaI.V drug userImmunosuppression due to either medication or HIVAlcohol excessInvestigations MRI is the imaging modality of choice, with a sensitivity of 90-100%ManagementFlucloxacillin 6 weeksClindamycin if penicillin-allergicAvascular necrosis of Hip(AVN) death of bone tissue 2ry to loss of blood supply bone destruction and loss of joint function most commonly affects the epiphysis of long bones ( femur).Causeslong-term steroid usechemotherapyalcohol excesstraumaFeaturesinitially asymptomaticPain in the affected joint might referred to groinLimping and limited range of joint mobility InvestigationPlain X- Ray May be normal initially. Osteopenia and microfractures may be seen early on. Collapse of the articular surface may result in the "Crescent Sign"MRI is the investigation of choice. It is more sensitive than radionuclide bone scanningManagement Joint replacement may be necessary DD. Bone metastasis X-ray lesions + bone pain.Hip pain in adultsConditionFeaturesOsteoarthritisPain exacerbated by exercise and relieved by restReduction in internal rotation is often the first signAge, obesity and previous joint problems are risk factorsInflammatory arthritisPain in the morningSystemic featuresRaised inflammatory markersGreater trochanteric pain syndrome (Trochanteric bursitis)Due to repeated movement of the fibroelastic iliotibial bandPain and tenderness over the lateral side of thigh↑↑ (Night & when ling on the affected side.↑↑ women aged 50-70 years.No limitation of movement X- Ray might reveal mild space narroingReferred lumbar spine painFemoral nerve compression cause referred pain in the hipFemoral nerve stretch test may be positive - lie the patient prone. Extend the hip joint with a straight leg then bend the knee. This stretches the femoral nerve and will cause pain if it is trappedMeralgia paraestheticaCaused by compression of lateral cutaneous nerve of thighTypically burning sensation over antero-lateral aspect of thighAvascular necrosisSymptoms may be of gradual or sudden onsetMay follow high dose steroid therapy or previous hip fracture of dislocationPubic symphysis dysfunctionCommon in pregnancyLigament laxity increases in response to hormonal changes of pregnancyPain over the pubic symphysis with radiation to the groins and the medial aspects of the thighs. A waddling gait may be seenTransient idiopathic osteoporosisAn uncommon condition sometimes seen in the third trimester of pregnancyGroin pain associated with a limited range of movement in the hipatients may be unable to weight bearESR may be elevatedMeralgia paraestheticaGreek words "Meros" thigh and "Algos" pain syndrome of paraesthesia in the distribution of the lateral femoral cutaneous nerve (LFCN). It is an entrapment mononeuropathy of the LFCN, but can also be iatrogenic after a surgical procedure, or result from a neuroma. Although uncommon, meralgia paraesthetica is not rare and is hence probably underdiagnosed.AnatomyThe LFCN is primarily a sensory nerve, carrying no motor fibres most commonly originates from the L2/3 segments.After passing behind the psoas muscle, it runs beneath the iliac fascia as it crosses the surface of the iliac muscle and eventually exits through or under the lateral aspect of the inguinal ligament.As the nerve curves medially and inferiorly around the anterior superior iliac spine (ASIS), it may be subject to repetitive trauma or pression of this nerve anywhere along its course can lead to the development of meralgia paraesthetica.Epidemiology30 and 40 W men > womenIn some, both legs may be affected.↑↑ D.M .Risk factors?ObesityPregnancyTense ascitesTraumaIatrogenic, pelvic osteotomy, spinal surgeries, laparoscopic hernia repair and bariatric surgery abduction splints (management of Perthe's D Various sports gymnastics, football, bodybuilding and strenuous exercise.Some cases are idiopathic.Presentation with the following symptoms in the upper lateral aspect of the thigh:?Burning, tingling, coldness, or shooting painNumbnessDeep muscle ache↑↑↑standing, and ↓↓↓sittingThey can be mild and resolve spontaneously or may severely restrict the patient for many years.Signs:Symptoms may be reproduced by deep palpation just below the ASIS (pelvic compression) and also by extension of the hip.There is altered sensation over the upper lateral aspect of the thigh.There is no motor weakness.Investigations:The pelvic compression test is highly sensitive, and often, meralgia paraesthetica can be diagnosed based on this test aloneInjection of the nerve with local anaesthetic will abolish the pain. Using ultrasound is effective both for diagnosis and guiding injection therapy Nerve conduction studies may be useful.Rotator cuff musclesSItS?- small t for teres minor ↑↑Pain (Movement, at night and when lying on the affected side)SupraspinatusInfraspinatusteres minorSubscapularisMuscleNotesSupraspinatusaBducts arm before deltoidMost commonly injuredInfraspinatusRotates arm laterallyteres minoraDDucts & rotates arm laterallySubscapularisaDDuct & rotates arm mediallyElbow painConditionNotesLateral epicondylitis (Tennis elbow)45-55 years dominant arm activity (house painting or playing tennis)Pain and tenderness localised to the lateral epicondyle↑↑ ( resisted wrist extension + elbow extended) OR (supination of the forearm + elbow extended)Attacks ( 6 Ms -2 years) W acute pain for 6-12 weeksManagement optionsadvice on avoiding muscle overloadsimple analgesiasteroid injectionphysiotherapyRadial tunnel syndromeCompression of the posterior interosseous branch of the radial nerve. overuse.symptoms are similar to lateral epicondylitis making it difficult to diagnoseDD. 4-5 cm distal to the lateral epicondyle↑↑ by extending the elbow + pronating the forearmMedial epicondylitis (golfer's elbow)pain and tenderness localised to the medial epicondyle↑↑ wrist flexion and pronationnumbness / tingling in the 4th and 5th finger due to ulnar nerve involvementCubital tunnel syndromeCompression of the ulnar nerve.↑↑ elbow is resting on a firm surface OR flexed for extended periodslater numbness in the 4th and 5th finger with associated weaknessOlecranon bursitisSwelling over the posterior aspect of the elbow. middle-aged male patientspain, warmth and erythema.Adhesive capsulitis(frozen shoulder) is a common cause of shoulder pain. It is most common in middle-aged females. The aetiology is not fully understood.Associations D.M up to 20% of diabetics may have an episode of frozen shoulderFeatures typically develop over daysExternal rotation is affected > internal rotation or abduction↓↓( active and passive movement) Painful freezing phase Adhesive phase Recovery phaseBilateral (20%) Episode between 6 months and 2 yearsThe?diagnosis is usually clinical?although imaging may be required for atypical or persistent symptoms.ManagementNo single intervention has been shown to improve outcome in the long-termTreatment options include NSAIDs, physiotherapy, oral corticosteroids and intra-articular corticosteroidsCarpal tunnel syndrome (Thumb and index)Compression of median nerve in the carpal tunnel. Featurespain/pins and needles in Thumb, index, middle fingerunusually the symptoms may 'ascend' proximallypatient shakes his hand to obtain relief, classically at nightExaminationweakness of thumb abduction (abductor pollicis brevis)wasting of thenar eminence (NOT hypothenar)Tinel's sign Tapping causes paraesthesiaPhalen's sign flexion of wrist causes symptomsCausesidiopathicpregnancyoedema heart failureObesity ?independent risk factor in those < 63 yearslunate fracturerheumatoid arthritisElectrophysiologymotor + sensory: prolongation of the action potentialTreatmentcorticosteroid injectionwrist splints at nightsurgical decompression (flexor retinaculum division)C6 entrapment neuropathy More proximal (weakness of the biceps muscle or reduced biceps reflex).Cubital Tunnel Syndrome(little &Ring finger)Due to compression of the ulnar nerve as it passes through the cubital tunnel.?FeaturesTingling and numbness of the 4th and 5th finger?which starts off intermittent and then becomes constant.Over time patients may also develop weakness and muscle wastingPain worse on leaning on the affected elbowOften a history of osteoarthritis or prior trauma to the area.Investigationsthe diagnosis is usually clinicalhowever, in selected cases nerve conduction studies may be usedManagement?Avoid aggravating activityPhysiotherapySteroid injectionsSurgery in resistant casesRadial tunnel syndrome aching and paraesthesia of the hand with forearm pain distal to the lateral epicondyle?De Quervain's tenosynovitis Base of thumb/Radial styloid common condition Inflammation of sheath containing the extensor pollicis brevis and abductor pollicis longus tendons. females 30 - 50 years Featurespain on the radial side of the wristtenderness over the radial styloid processabduction of the thumb against resistance is painfulFinkelstein's test the examiner pulls the thumb of the patient in ulnar deviation and longitudinal traction. pain over the radial styloid process and along the length of extensor pollisis brevis and abductor pollicis longusManagementanalgesiasteroid injectionimmobilisation with a thumb splint (spica) may be effectivesurgical treatment is sometimes requiredAnkle injury: Ottawa rulesThe Ottawa Rules with for ankle X-Rays (sensitivity 100%)An ankle x-ray only if there is any pain in the malleolar zone + 1 of the following findings:Bony tenderness lateral malleolar zone (tip of the lateral malleolus to include the lower 6 cm of posterior border of the fibular)bony tenderness medial malleolar zone (from the tip of the medial malleolus to the lower 6 cm of the posterior border of the tibia)inability to walk 4 weight bearing steps immediately after the injury and in the emergency departmentThere are also Ottawa rules available for both foot and knee injuriesFamilial Mediterranean Fever "Recurrent Polyserositis" AR (2nd decade. ↑↑↑Turkish, Armenian and Arabic descent)Features - attacks typically last 1-3 dayspyrexiaabdominal pain (due to peritonitis)pleurisypericarditisarthritisErysipeloid rash on lower limbsManagementColchicine may helpDD. Other PolyserositisPancreatitis1ry effusion lymphoma Lymphadenopathy, 1ry effusion lymphomaSLECastleman's? ................
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